Nutrition Gaps Raise Safety Concerns as Use of GLP-1 Weight Loss Drugs Accelerates
Key Takeaways:
- Many people prescribed GLP-1 weight loss medications receive little or no structured nutritional guidance, increasing the risk of preventable vitamin and mineral deficiencies and loss of muscle mass.
- New research highlights a lack of high-quality evidence on how diet quality, protein intake, and micronutrient intake are affected during treatment with drugs such as semaglutide and tirzepatide.
- Experts warn that without integrated nutritional care, the rapid expansion of GLP-1 drug use could undermine long-term health benefits despite effective weight loss.
Experts from University College London and the University of Cambridge are warning that many people prescribed newer weight loss medications may not be receiving sufficient nutritional guidance to support safe and sustainable weight loss. As a result, some individuals may face avoidable risks, including vitamin and mineral deficiencies and loss of lean body mass, particularly muscle.
The concerns arise from new research published in Obesity Reviews. Led by Dr Marie Spreckley of the University of Cambridge, the review identified limited high-quality evidence on how nutritional advice influences calorie intake, body composition, protein consumption, and patient experiences among people using these medications.
How GLP-1 weight loss drugs work
Drugs such as semaglutide and tirzepatide, sold under brand names including Ozempic, Wegovy, and Mounjaro, work by mimicking the action of glucagon-like peptide-1 (GLP-1). This hormone is released after eating and plays a role in regulating appetite and glucose metabolism. By enhancing feelings of fullness, reducing hunger, and dampening food cravings, these medications can substantially lower energy intake.
Studies suggest that calorie intake may fall by 16–39%, helping to explain why these drugs are highly effective for people living with obesity or overweight. However, the researchers note that there has been very little detailed study of how such reductions affect overall diet quality, protein intake, or micronutrient intake, including vitamins and minerals. Existing evidence indicates that lean body mass, including muscle tissue, can account for as much as 40% of total weight lost during treatment.
Experts warn of risks without nutrition support
Dr Adrian Brown, an NIHR Advanced Fellow at UCL’s Centre of Obesity Research and the study’s corresponding author, described how these medications alter eating behaviour.
“Obesity management medications work by suppressing appetite, increasing feelings of fullness, and altering eating behaviors, which often leads people to eat significantly less. This can be highly beneficial for individuals living with obesity, as it supports substantial weight loss and improves health outcomes.
“However, without appropriate nutritional guidance and support from healthcare professionals, there is a real risk that reduced food intake could compromise dietary quality, meaning people may not get enough protein, fiber, vitamins, and minerals essential for maintaining overall health.”
Without structured support, reduced intake may unintentionally lead to inadequate consumption of nutrients needed to preserve muscle mass, bone health, immune function, and overall physical resilience.
Public guidelines versus private use
Guidance from the National Institute for Health and Care Excellence recommends semaglutide for weight management only for people who meet strict eligibility criteria, such as a body mass index of at least 35.0 kg/m² alongside obesity-related comorbidities including type 2 diabetes or cardiovascular disease. When prescribed through the NHS, the medication is intended to be delivered as part of a comprehensive programme that includes dietary changes and increased physical activity.
In reality, most people currently using GLP-1 drugs in the UK obtain them outside the NHS. An estimated 1.5 million people are now using these medications, with around 95% accessing them through private providers. In these settings, ongoing nutritional advice and follow-up support are not always consistently offered.
Rising use outpaces nutrition guidance
Dr Spreckley, who works at the Medical Research Council Epidemiology Unit at the University of Cambridge, said nutritional care has not kept pace with the rapid uptake of these therapies.
“Use of GLP-1 receptor agonist therapies has increased rapidly in a very short period of time, but the nutritional support available to people using these medications has not kept pace. Many people receive little or no structured guidance on diet quality, protein intake, or micronutrient adequacy while experiencing marked appetite suppression.
“If nutritional care is not integrated alongside treatment, there’s a risk of replacing one set of health problems with another, through preventable nutritional deficiencies and largely avoidable loss of muscle mass. This represents a missed opportunity to support long-term health alongside weight loss.”
Low intakes of essential vitamins and minerals are associated with fatigue, impaired immune function, hair loss, and increased risk of osteoporosis. Loss of lean mass, most commonly muscle, can also raise the likelihood of weakness, injuries, and falls, particularly in older adults.
Limited research leaves major questions unanswered
The review identified only 12 studies that examined diet and nutritional outcomes alongside treatment with semaglutide or tirzepatide. These studies differed widely in how dietary advice was delivered and how nutritional outcomes were measured. Many lacked standardised methods and consistent reporting, making it difficult to draw firm conclusions about best practice.
Despite the rapid expansion of GLP-1 drug use, the researchers found little robust evidence to guide clinicians on how to support people nutritionally during treatment.
Lessons from bariatric nutrition care
Given the urgent need for practical guidance, the researchers suggest that interim lessons could be drawn from nutritional care used after bariatric surgery. Procedures such as gastric banding and gastric bypass lead to similar reductions in appetite and food intake.
Dr Cara Ruggiero, a co-author from the MRC Epidemiology Unit at the University of Cambridge, said established post-surgery principles could help address current gaps.
“While GLP-1 receptor agonists are increasingly used, there remains a clear gap in structured nutritional guidance. In the interim, we can draw on well-established post-bariatric nutrition principles. Our previous work highlights the importance of prioritizing nutrient-dense foods including high-quality protein intake, ideally distributed evenly across meals, to help preserve lean mass during periods of reduced appetite and rapid weight loss.”
Equipping healthcare professionals with the nutritional knowledge to guide patients safely through this kind of rapid weight loss is the focus of professional training such as the College of Contemporary Health’s Nutrition & Weight Management Essentials, a CPD-accredited online short course.
The available evidence did not support recommending strict low-fat diets alongside GLP-1 therapies. However, some observational studies reported that people using these medications consumed relatively high amounts of total and saturated fat, suggesting a potential need for personalised guidance that aligns with national dietary recommendations.
Meal timing was rarely examined in clinical trials. Nevertheless, the researchers note that eating smaller meals more frequently may help manage side effects such as nausea and improve tolerability, particularly during the early stages of treatment.
Studying real-world experiences
The research team also emphasised the importance of incorporating the perspectives of people using GLP-1 medications into future studies. Understanding what types of information and support individuals find most helpful could improve real-world care and long-term outcomes.
To address this, the team has launched AMPLIFY – Amplifying Meaningful Perspectives and Lived experiences of Incretin therapy use From diverse communitY voices. The project aims to explore how people experience next-generation weight loss medications in everyday life.
“These medications are transforming obesity care, but we know very little about how they shape people’s daily lives, including changes in appetite, eating patterns, well-being, and quality of life,” Dr Spreckley said. “That’s what we’ll explore, working in particular with people from communities historically under-represented in obesity research, to help shape the future of obesity treatment.”
The research was funded by the National Institute for Health and Care Research, with additional support from the Medical Research Council and the NIHR UCLH Biomedical Research Centre.
CCH insights:
GLP-1 medications are licensed for the treatment of diabetes and obesity and they should be used alongside diet and lifestyle advice to improve cardiometabolic health. However, they are now commonly known as ‘weight loss drugs’, implying their primary aim is for people to lose weight. But this is kind of missing the point – the weight loss outcome is one of the mediating effects of the drugs which leads to improved health. However, if weight loss is not accompanied by a move to a healthy diet, which provides adequate levels of essential nutrients, then health outcomes will be compromised, as highlighted by this study then health outcomes will be compromised, as highlighted by this study. Closing that gap starts with clinicians themselves being confident in the fundamentals: CCH’s Nutrition & Weight Management Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) gives healthcare professionals a solid grounding in nutrition and weight management, including how to help patients meet their protein and micronutrient needs and preserve lean muscle during weight loss.
Explore Nutrition & Weight Management Essentials →
GLP-1 Receptor Agonists Linked to Lower Mortality After Diabetic Foot Ulcers, Nationwide French Study Finds
Key Takeaways:
- Nearly one in seven people experienced death within one year of a first diabetic foot ulcer, highlighting the severity of risk following ulcer onset.
- Treatment with GLP-1 receptor agonists was independently associated with improved survival, including after major lower-limb amputation.
- Multidisciplinary care and early specialist involvement were associated with better outcomes, reinforcing the importance of structured follow-up.
Background and study aims
Diabetic foot ulcers remain one of the most serious complications of diabetes, often signalling advanced disease and a high burden of comorbidity. Despite advances in diabetes care, mortality following a first diabetic foot ulcer continues to be substantial.
This nationwide observational study set out to identify factors associated with one-year mortality after a first recorded diabetic foot ulcer using data from the French National Health Data System (SNDS). A secondary objective was to examine mortality within one year following major lower-limb amputation in the same population.
Study design and data sources
Researchers conducted a retrospective cohort analysis using the SNDS, a comprehensive national database that captures hospital admissions, outpatient care, prescribed medications, and long-term disease registrations across France.
Adults with a first incident diabetic foot ulcer recorded between January 2017 and December 2018 were included. Case identification combined hospital discharge diagnoses and community care records, allowing capture of people diagnosed both in hospital and in outpatient settings. All individuals were followed for 12 months after ulcer identification.
To examine associations with mortality, the researchers used Cox proportional hazards models. These models adjusted for a wide range of variables, including demographic characteristics, clinical comorbidities, diabetes treatments, major amputation, and access to specialist care.
Mortality and amputation outcomes
In total, 133,791 people with a first diabetic foot ulcer were identified. Within one year of diagnosis, 14.6% died, underlining the high short-term mortality associated with this complication. During the same period, 3.5% underwent a major lower-limb amputation.
Outcomes following amputation were particularly poor. Among those who had a major amputation, 28.8% died within one year, indicating a markedly elevated risk compared with people who did not undergo amputation.
Factors associated with increased mortality
Several factors were independently associated with a higher risk of death within one year of a first diabetic foot ulcer. These included male sex, increasing age, and ulcers identified during a hospital admission rather than in the community.
Clinical and treatment-related predictors of higher mortality included insulin use, major lower-limb amputation, and a range of comorbid conditions. Cardiovascular disease, cancer, dementia, end-stage kidney disease, and liver disease were all strongly associated with poorer survival.
Similar patterns were observed when analysing mortality after major amputation, suggesting that underlying health status and disease severity play a central role in outcomes across the care pathway.
Protective factors and the role of GLP-1 receptor agonists
Several factors were associated with a lower risk of death. Use of lipid-lowering therapy emerged as a protective factor, as did prior contact with specialist healthcare professionals. People who had consulted diabetologists, ophthalmologists, or podiatrists before ulcer onset experienced better survival, pointing to the benefits of ongoing, multidisciplinary diabetes care.
Notably, treatment with glucagon-like peptide-1 receptor agonists was independently associated with reduced mortality at one year. This association persisted both in the overall cohort and among people who underwent major lower-limb amputation, suggesting a consistent survival benefit linked to this class of medication.
Interpretation and implications for care
The findings confirm that one-year mortality after a diabetic foot ulcer remains unacceptably high and is closely linked to age, comorbidity burden, and disease severity. Importantly, the inclusion of community-identified ulcers highlights that people with diabetic foot disease are highly vulnerable even outside hospital settings.
The observed association between GLP-1 receptor agonist use and improved survival adds to growing evidence that these therapies may offer benefits beyond glycaemic control. Alongside pharmacological treatment, structured follow-up and early involvement of specialist services appear to play a critical role in improving outcomes.
Conclusions
This nationwide study shows that mortality following a first diabetic foot ulcer is substantial, particularly among people with advanced comorbidities and those requiring major amputation. Glucagon-like peptide-1 receptor agonists and coordinated, multidisciplinary care were associated with better survival and should be prioritised in high-risk populations.
Together, these findings underscore the urgent need to strengthen preventive strategies, optimise care pathways, and ensure timely access to specialist diabetes and foot care services for people living with diabetes who are at risk of ulceration.
Read More
Combination of Hormone Therapy and Tirzepatide Linked to Greater Weight Loss After Menopause, Study Finds
Key Takeaways:
- Postmenopausal women using menopausal hormone therapy alongside tirzepatide lost around 35% more weight than those using tirzepatide alone in an observational study.
- The findings suggest a potential interaction between hormone therapy and GLP-1-based obesity medications, although causality cannot be confirmed.
- Researchers say the results warrant randomised clinical trials to explore mechanisms and broader cardiometabolic effects.
Weight management challenges after menopause
A new study led by researchers at Mayo Clinic suggests that combining menopausal hormone therapy with tirzepatide may be associated with substantially greater weight loss in postmenopausal women. The findings, published in The Lancet Obstetrics, Gynaecology, & Women’s Health, indicate that women receiving hormone therapy lost around 35% more weight while taking tirzepatide compared with those treated with tirzepatide alone.
Tirzepatide is approved by the US Food and Drug Administration for the treatment of overweight and obesity. The study’s authors say the results could expand treatment options for the many women who experience weight gain and related health risks following menopause.
Menopause is associated with accelerated age-related weight gain and a higher likelihood of developing overweight or obesity, both of which are major risk factors for cardiovascular disease, type 2 diabetes, and other long-term conditions. In addition to changes in body weight, the decline in oestrogen levels that occurs during menopause is also linked to physiological changes that may independently increase cardiovascular risk.
“This study provides important insights for developing more effective and personalized strategies for managing cardiometabolic risk in postmenopausal women,” says Regina Castaneda, MD, postdoctoral research fellow at Mayo Clinic and first author of the study.
Hormone therapy and obesity treatments
Menopausal hormone therapy is considered the most effective first-line treatment for common menopausal symptoms, such as hot flashes and night sweats, which affect up to 75% of postmenopausal women. Despite its widespread use, evidence on how hormone therapy may interact with pharmacological obesity treatments remains limited.
Previous research has suggested that postmenopausal women using hormone therapy may experience greater weight loss when treated with semaglutide, another GLP-1-based medication for obesity. However, until now, no studies had specifically examined whether hormone therapy might influence outcomes in people treated with tirzepatide.
To explore this question, Dr Castaneda and colleagues reviewed data from 120 participants with overweight or obesity who had received tirzepatide for weight management for at least 12 months. Outcomes among participants who were also using menopausal hormone therapy were compared with those of participants with similar characteristics who were not receiving hormone therapy.
Findings and limitations
According to the researchers, women using both treatments experienced markedly greater weight loss than those using tirzepatide alone.
“In this observational study, women who used menopausal hormone therapy lost about 35% more weight than women taking tirzepatide alone. Because this was not a randomized trial, we cannot say hormone therapy caused additional weight loss,” says Maria Daniela Hurtado Andrade, MD, PhD, endocrinologist at Mayo Clinic and senior author of the study.
She adds that other factors may partly explain the difference observed between the groups.
“It is possible that women using hormone therapy were already engaged in healthier behaviors, or that menopause symptom relief improved sleep and quality of life, making it easier to stay engaged with dietary and physical activity changes.”
The authors emphasise that, as an observational analysis, the study cannot establish a causal relationship between hormone therapy and enhanced weight loss. Nonetheless, they argue that the size of the observed difference is clinically meaningful.
Possible biological synergy
Dr Castaneda notes that the findings align with emerging preclinical evidence suggesting a biological interaction between oestrogen and GLP-1-based therapies.
“The magnitude of this difference warrants future studies that could help clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact. Interestingly, preclinical data suggest a potential synergy, with estrogen appearing to enhance the appetite-suppressing effects of GLP-1,” she says.
Such a mechanism could help explain why women receiving hormone therapy appeared to derive additional benefit from tirzepatide in this study.
Next steps for research
The research team plans to build on these findings through more rigorous study designs.
“Next, we plan to test these observations in a randomized clinical trial and determine if benefits extend beyond weight loss – specifically, whether hormone therapy also enhances the effects of these medications on cardiometabolic measures,” says Dr Hurtado Andrade. “If confirmed, this work could speed the development and adoption of new, evidence-based strategies to reduce this risk for millions of postmenopausal women navigating this life stage.”
The study was funded by the Mayo Clinic Center for Women’s Health Research. The full publication includes a complete list of authors, disclosures, and funding sources.
CCH insight:
This is an interesting study, but as the authors state, no conclusions can be drawn from the findings. But it does raise many questions about the possible potential synergistic effects of oestrogen and GLP-1 therapy. Establishing whether cardiometabolic benefits of GLP-1 medications are amplified, as well as weight loss, should be a priority.
Read More
New Evidence Suggests GLP-1 Drugs May Improve Survival in Severe Psychiatric Disorders
Key Takeaways:
- People living with serious mental illnesses experience substantial excess cardiometabolic risk and premature mortality, driven largely by cardiovascular disease rather than psychiatric symptoms alone.
- GLP-1 receptor agonists may help narrow this mortality gap by targeting obesity, diabetes, cardiovascular disease, and renal disease rather than replacing established psychiatric treatments.
- While promising, the use of GLP-1 receptor agonists in people with serious mental illness requires careful attention to safety, access, cost, and equitable allocation.
A recent editorial published in Expert Opinion on Pharmacotherapy explored the emerging role of glucagon-like peptide-1 receptor agonists in improving survival and long-term health outcomes for people living with serious mental illnesses. The authors emphasised that these medicines are unlikely to replace established psychiatric therapies. Instead, their greatest potential lies in addressing the cardiometabolic drivers of excess morbidity and mortality that disproportionately affect this population.
The editorial situates GLP-1 receptor agonists within a broader public health context, arguing that interventions capable of extending healthspan and reducing cardiovascular mortality are urgently needed for people with serious mental illness.
Development and expanding indications of GLP-1 receptor agonists
The first GLP-1 receptor agonist, exenatide, received approval from the United States Food and Drug Administration in 2005 for the treatment of type 2 diabetes. Since that time, multiple GLP-1 mono-agonists have been approved, alongside tirzepatide, the first dual agonist targeting both the GLP-1 and glucose-dependent insulinotropic polypeptide receptors. Additional dual and triple agonists acting on GLP-1, GIP, and glucagon receptors are now in late-stage clinical development.
While initially developed for glycaemic control in type 2 diabetes, GLP-1 receptor agonists now have indications that extend well beyond glucose lowering and weight management in people living with overweight or obesity. Approved uses include treatment of metabolic dysfunction-associated steatohepatitis in people with moderate or advanced fibrosis, management of obstructive sleep apnoea in adults with obesity, reduction of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, and slowing the progression of chronic kidney disease while reducing cardiovascular mortality in people living with both chronic kidney disease and type 2 diabetes.
Oral formulations are also expanding. Oral semaglutide is already available, and synthetic small-molecule oral GLP-1 receptor agonists are expected to receive approval in 2026. These formulations may help address barriers related to injectable delivery, manufacturing complexity, supply chains, and access. There is now broad consensus that GLP-1 receptor agonists have transformed the management of metabolic disease and are associated with reductions in renal disease progression, cardiovascular events, and mortality among people with metabolic disorders.
Cardiometabolic burden in serious mental illness
Conditions such as schizophrenia, major depressive disorder, bipolar disorder, and related serious mental illnesses are severe, prevalent, and often lifelong. They are major contributors to disability, reduced healthspan, and diminished social and economic participation, particularly among younger adults.
People living with serious mental illness experience markedly premature and excess mortality. Estimates of years of life lost typically range from five to twenty-five years, with cardiovascular disease accounting for the majority of this gap. Earlier onset of cardiometabolic conditions, higher prevalence of obesity and diabetes, and cumulative exposure to cardiometabolic risk factors all contribute to this disparity.
Each condition currently treated with GLP-1 receptor agonists contributes differently to cardiometabolic risk in this population. In parallel, several agents in mid- and late-stage development target chronic diseases such as peripheral artery disease and atherosclerotic heart disease, conditions that disproportionately affect people living with serious mental illness.
Limitations of current psychiatric treatments on mortality
Although antipsychotics, antidepressants, mood stabilisers, and anticonvulsants are clinically effective for managing psychiatric symptoms, their impact on healthspan and cardiovascular mortality has been limited. Demonstrated reductions in mortality have been confined to selected classes and agents, including second-generation long-acting antipsychotics, lithium, and clozapine.
Lithium, despite strong evidence of efficacy in bipolar disorder and potential mortality benefits, remains under-prescribed. This limits its overall public health impact and underscores the need for complementary strategies that directly address physical health outcomes alongside psychiatric symptom control.
Current and emerging clinical applications in psychiatric populations
GLP-1 receptor agonists are already recommended for managing weight gain associated with psychotropic medications when discontinuation or switching of psychiatric treatment is not feasible. This indication is particularly relevant given the high prevalence of medication-associated weight gain in people living with serious mental illness.
Preliminary evidence also suggests a potential protective effect against lithium-induced nephrotoxicity, a complication for which no approved therapy currently exists. In addition, several GLP-1 receptor agonists are being developed or repurposed for the treatment of alcohol, tobacco, and opioid use disorders.
Beyond metabolic outcomes, preclinical studies, small controlled trials, and observational research suggest that GLP-1 receptor agonists may exert beneficial effects on mood disorders and on specific psychopathology domains that significantly impair quality of life, including cognitive dysfunction and anhedonia. While these findings remain early, they point to possible neuropsychiatric benefits that warrant further investigation.
Safety considerations in people living with serious mental illness
Several safety considerations are particularly relevant in this population. Gastrointestinal side effects, including constipation, may interact with pre-existing gastrointestinal motility disturbances caused by psychotropic medications.
Clinicians should also consider the elevated risks of pancreatitis and sarcopenia, both of which disproportionately affect people living with serious mental illness. Renal function requires particular attention, as GLP-1 receptor agonists that are primarily renally eliminated, such as lixisenatide and exenatide, are contraindicated in severe renal disease, which is more prevalent in this group.
Early pharmacovigilance reports raised concerns about a possible association between GLP-1 receptor agonists and suicidality. However, larger subsequent studies have not demonstrated a causal relationship. Continued monitoring remains advisable, particularly in populations already at increased risk of suicidal ideation and behaviour.
Navigating these considerations well – patient selection, contraindications, side-effect management and monitoring – is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Practice: Prescribing, a CPD-accredited online short course.
Implications for healthspan and mortality reduction
People living with serious mental illness account for a disproportionate share of years of life lost and disability-adjusted life years worldwide. Despite decades of progress in psychopharmacology, the mortality gap between this population and the general population has not meaningfully narrowed.
Therapeutic strategies that directly reduce mortality and extend healthspan are therefore urgently required. In this context, GLP-1 receptor agonists represent one of the most promising pharmacological classes currently available. Their potential impact will depend on addressing persistent challenges related to cost, reimbursement policy, equitable access, and ongoing supply constraints.
Prioritising people living with serious mental illness within fair allocation frameworks could help reduce excess and premature mortality in this vulnerable population in the near term, while longer-term evidence continues to emerge.
CCH insight
This emerging evidence points to real promise for a group facing a stark mortality gap – but realising it safely depends on clinicians who are confident using GLP-1 medications well, particularly in patients with complex comorbidities. CCH’s GLP-1RAs in Practice: Prescribing CPD short course (2 CPD hours, fully online, CPD-accredited) equips prescribers to get every part of the consultation right, from patient selection and contraindications through to titration, side-effect management and monitoring.
Explore GLP-1RAs in Practice: Prescribing →
More Than One in Four Adults Worldwide May Be Eligible for GLP-1 Weight-Loss Medicines, Global Analysis Suggests
Key Takeaways:
- More than 27 percent of adults globally may be eligible for GLP-1 receptor agonists for weight management, based on pooled data from 99 countries.
- Eligibility is highest among women, older adults, and people living in low- and middle-income countries, raising significant questions around access and health equity.
- Researchers emphasise that medicines alone are not sufficient, and sustained investment in prevention and non-pharmacological obesity care remains essential.
A growing global obesity challenge
The worldwide prevalence of obesity has more than doubled over the past three decades, accompanied by sharp rises in weight-related conditions such as type 2 diabetes, cardiovascular disease, and several cancers. This escalating public health challenge places increasing strain on healthcare systems and national economies across the globe.
Against this backdrop, a new international study suggests that glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 medications, could play a substantial role in addressing obesity and its related complications at scale. The analysis was co-led by investigators from Mass General Brigham and aimed to estimate how many adults worldwide might benefit from these medicines.
Large-scale global data analysis
Researchers from Mass General Brigham collaborated with colleagues at Washington University School of Medicine in St. Louis and Emory University’s Rollins School of Public Health to pool household health survey data from 99 countries, collected between 2008 and 2021.
The final dataset included 810,635 adults aged 25 to 64 years, selected based on the availability of key clinical measures, including:
- Body mass index
- Blood pressure
- Diabetes biomarkers
- Diagnostic history of hypertension and diabetes
Eligibility for GLP-1 treatment was defined using established clinical thresholds. Adults were considered eligible if they had:
- A BMI greater than 30, or
- A BMI greater than 27 in the presence of hypertension, diabetes, or both
One in four adults eligible worldwide
Using these criteria, the researchers found that 27 percent of adults globally would be eligible for GLP-1 medications for weight management. Notably, around four-fifths of eligible individuals lived in low- and middle-income countries, highlighting a potential mismatch between need and access.
Eligibility varied substantially by region:
- Europe and North America showed the highest rates at 42.8 percent
- The Pacific Islands followed closely at 41.0 percent
Differences were also observed across demographic groups:
- Women were more likely to be eligible than men, at 28.5 percent versus lower rates among men
- Older adults showed markedly higher eligibility at 38.3 percent, compared with 17.9 percent among younger adults
The findings were published as a research letter in The Lancet Diabetes & Endocrinology.
Rethinking obesity through biology
Commenting on the findings, co-senior author Jennifer Manne-Goehler, MD, ScD, a physician at Brigham and Women’s Hospital and Mass General Brigham, highlighted the paradigm shift represented by GLP-1 therapies.
“There has never been such a potentially transformational and scalable tool for obesity, type 2 diabetes, and other health-related complications of obesity.”
She also reflected on the historical framing of obesity as a personal failing rather than a biologically driven disease.
“For so many decades, we told everyone the problem was you – you need to move more and eat less, then you will not struggle with this problem. GLP-1 receptor agonists have allowed us to really understand that biology is much more powerful than that, and ‘eat less, move more’ is just an oversimplified way to think about things.”
Global interest meets practical constraints
The potential of GLP-1 medicines has already been recognised by the World Health Organization, which is actively exploring ways to make these treatments more widely available as standard therapies. However, translating this promise into real-world impact depends on understanding the scale of need and addressing significant barriers to access.
Corresponding author Sang Gune K. Yoo, MD, who conducted the work while a research fellow in cardiology at Washington University School of Medicine, noted that the findings were consistent with global obesity trends.
“Given the steadily increasing prevalence of obesity, it is not surprising that our analysis found that more than one quarter of adults around the world may be eligible for this medication.”
He cautioned, however, that important questions remain unanswered.
“This medication has the potential to help many individuals, although further research is needed to better understand its long-term safety and sustainability. Access remains a major challenge as these medications are difficult to obtain in many settings. Most importantly, we must continue to invest in and develop effective non-pharmacological strategies for the prevention and treatment of obesity, an area where substantial gaps remain.”
Equity at the centre of global implementation
The study also underscores profound equity considerations. Eligibility was disproportionately high among women and people living in regions with limited healthcare resources.
Manne-Goehler highlighted the urgency of addressing these disparities.
“These socioeconomic and gender eligibility percentiles are especially staggering. As of last year, type 2 diabetes was the top cause of death for women in South Africa. There are parts of the world where women can really benefit from these medicines, and it is our job to see through their implementation.”
Co-lead author Felix Teufel, MD, from Emory University’s Rollins School of Public Health, framed access to GLP-1 therapies as a broader ethical issue.
“Global access to GLP-1s is a question of health equity. The goal is to ensure large-scale access for people who would benefit most – not just those easiest to reach.”
Beyond medicines alone
While the findings point to a potentially transformative role for GLP-1 medications in global obesity care, the authors stress that pharmacological approaches cannot replace comprehensive prevention and treatment strategies. Addressing obesity at scale will continue to require sustained investment in public health, supportive environments, and evidence-based, non-pharmacological interventions alongside new medical therapies.
CCH insight:
This study reminds us of the scale of the obesity pandemic. There are more than 1 billion people estimated to be living with obesity, according to the World Health Organisation – most of whom could in theory benefit from GLP-1 medications. The priority should be to provide access for those who are in greatest need, rather than those who can afford to pay for them. The development of oral GLP-1s is a big step, as this will increase access and bring prices down, but there is a very long way to go.
Read More
GLP-1 Weight-Loss Medications Linked to Fewer Severe Asthma Attacks in Adolescents with Excess Weight
Key Takeaways:
- Adolescents with excess weight and asthma who were prescribed GLP-1 medications experienced around half as many asthma-related emergency room visits over one year compared with peers not taking these drugs.
- Use of GLP-1 therapies was also associated with reduced reliance on steroids and rescue inhalers, suggesting improved asthma control.
- Researchers suggest these medicines may offer a dual benefit, supporting weight management while lowering the risk of asthma exacerbations in this population.
Study suggests dual benefit for weight and asthma control
Severe asthma attacks among adolescents with excess weight may be significantly reduced with the use of newer weight-loss medications such as Ozempic and Zepbound, according to a new observational study.
The research found that emergency room visits for asthma were cut by more than half among teenagers who were prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. The findings were reported on 29 December in JAMA Network Open.
“Our findings suggest a potential dual benefit for this population, where a single class of medication could address both weight management and lower risk for asthma exacerbation, thereby potentially reducing the burden of two common and interconnected chronic conditions,” the researchers concluded.
The study was led by Dr Lin‑Shien Fu, chief of paediatric nephrology and immunology at Taichung Veterans General Hospital.
How the study was conducted
Researchers followed 1,070 adolescents aged 12 to 18 years who were living with excess weight and had a clinical diagnosis of asthma. Approximately half of the group had been prescribed a GLP-1 medication, while the remainder had not received a weight-loss drug.
GLP-1 receptor agonists mimic the naturally occurring GLP-1 hormone, which plays a role in regulating insulin and blood glucose levels. These medicines also reduce appetite and slow gastric emptying, contributing to weight loss.
Over a 12-month follow-up period, the researchers recorded:
- Eight asthma-related emergency department visits among adolescents taking a GLP-1 medication
- Nineteen asthma-related emergency visits among those not prescribed a weight-loss drug
Reduced need for asthma medications
In addition to fewer emergency visits, adolescents taking GLP-1 medications were less likely to require other treatments for asthma control.
The study found that:
- 21% of adolescents taking a GLP-1 medication required steroid treatment for asthma, compared with 31% of those not taking the drugs
- 32% of adolescents in the GLP-1 group needed a rescue inhaler, compared with 45% in the non-GLP-1 group
These differences suggest an overall reduction in asthma severity and symptom burden among those prescribed GLP-1 therapies.
Weight loss and inflammation may explain the findings
Experts not involved in the research say the observed improvements are likely linked to the degree of weight loss achieved with these newer medications.
Dr Michelle Katzow, medical director of the POWER Kids Weight Management Program and associate professor of paediatrics at Cohen Children’s Medical Center in New York City, commented on the findings in a news release.
“I think it is not surprising and not so new, except for the degree of weight loss that the drug induces is so much bigger in magnitude than we have seen before,” she said.
Dr Katzow explained that excess weight contributes to systemic inflammation, which can worsen asthma symptoms and increase the likelihood of exacerbations.
“The sort of inflammation associated with obesity predisposes somebody to having worse asthma or worse symptoms of asthma,” she said.
“If you can help people lose enough weight by whatever means, then you can improve their asthma severity.”
Implications for adolescents struggling with appetite control
Dr Katzow added that GLP-1 medications may be particularly helpful for adolescents who struggle to adopt healthy behaviours because of persistent hunger.
She noted that this is a common challenge among young people with excess weight.
“And that is true for a lot of kids,” she said. “They are just really hungry and they are thinking about food a lot. Trying to make healthier choices or eat less is really hard to do if you are hungry all the time.”
A cautious but promising signal
While the study does not establish a direct causal relationship, it adds to growing evidence that weight-loss interventions can have meaningful benefits beyond body weight alone. The findings suggest that, for some adolescents living with excess weight and asthma, GLP-1 receptor agonists may help reduce the frequency and severity of asthma exacerbations alongside supporting weight management.
Further research will be needed to confirm these findings and to better understand the long-term safety and clinical role of GLP-1 therapies in paediatric populations.
CCH insight:
The long list of benefits of GLP-1 therapy continues to grow. If obesity increases the risk of asthma, it is not surprising that GLP-1 therapy results in a reduction in hospital visits due to asthma. Further studies are needed to back up these results, and also to see if the same benefits are seen in adults, as well as adolescents.
Read More
Wegovy Oral Obesity Treatment Launches in US Pharmacies Following FDA Approval
Key Takeaways:
- The oral form of Wegovy has launched in pharmacies, with the starting dose available now and higher doses expected shortly.
- Clinical trial data show weight loss outcomes comparable to the injectable version when taken as prescribed alongside dietary and activity changes.
- Pricing varies significantly depending on dose and insurance coverage, with list prices matching the injectable formulation.
Oral Wegovy becomes available nationwide
The oral form of Wegovy launched on Monday, with the starting dose now available in pharmacies across the country. Higher doses are expected to arrive by the end of the week, according to reports accompanying the launch.
The pill was approved by the Food and Drug Administration on 22 December for the treatment of obesity. It is also approved to reduce the risk of heart attack and stroke in people who are living with obesity or who are overweight.
Building on the success of the injectable formulation
The launch of the pill follows the blockbuster success of Novo Nordisk’s injectable Wegovy, which has been available since 2021. Demand for the injection was so high that it remained in short supply until February 2025.
Novo Nordisk has positioned the oral formulation as an alternative for people who prefer not to use injections, while maintaining similar clinical effectiveness.
Evidence from clinical trials
Clinical trial data suggest that the oral version of Wegovy delivers weight loss results comparable to the injectable form. In a study published in the New England Journal of Medicine, participants taking a 25 milligram Wegovy pill experienced an average weight reduction of 13.6% over 64 weeks. By comparison, participants receiving a placebo lost an average of 2.2% of their body weight.
Novo Nordisk estimates that people who remain on treatment, reduce their calorie intake and engage in regular physical activity could achieve an average weight reduction of 16.6%.
How the pill is taken and side effects
Unlike the injectable formulation, the Wegovy pill must be taken on an empty stomach. People are advised to wait at least 30 minutes before eating or drinking anything else to ensure the medicine is properly absorbed.
The most commonly reported side effects are similar to those seen with the injection and include nausea, diarrhoea and vomiting.
Pricing and insurance coverage
When Novo Nordisk announced a drug pricing agreement with the Trump administration in November, the company stated that it would offer the obesity pill for $149 per month to people not using health insurance. This price applies only to the starting dose purchased directly by consumers. Higher doses will be priced at $299 per month under the same arrangement.
The list price, which is used to determine insurance coverage, is set at $1,349 per month. This matches the list price of the injectable Wegovy.
Insurance coverage for obesity medications became more restrictive in 2025, according to an analysis from GoodRx, a website that helps people find discounts on prescription medicines. Novo Nordisk has said that people with insurance coverage may be able to access the Wegovy pill for as little as $25 per month.
How Wegovy compares with other oral GLP-1 medicines
Although the Wegovy pill is the first oral obesity treatment of its kind to receive FDA approval, Novo Nordisk already markets an oral GLP-1 medicine for Type 2 diabetes called Rybelsus. Rybelsus contains the same active ingredient, semaglutide, but is prescribed at different doses and is not approved for obesity.
Competition in the oral obesity drug market may soon increase. Eli Lilly, the manufacturer of the Zepbound injection, applied to the FDA in late 2025 for approval of its own obesity pill. The agency granted the company a priority review voucher, with a regulatory decision expected as early as this year.
CCH insight:
Hopefully oral Wegovy will be available in the UK soon, and at a more affordable cost than the injectable version. And this will hopefully enable increased access to the drug on the NHS. The current, very limited availability of GLP-1 therapy on the NHS is costing the UK tax-payer, because the cost of treating the complications and consequences of obesity is much greater than the cost of treating obesity – GLP-1s not only lead to weight loss, they reduce the risk of diabetes, heart disease, kidney disease and possibly many other conditions.
Read More
GLP-1 Receptor Agonists Unlikely to Meaningfully Influence Obesity-Related Cancer Risk, Review Suggests
Key Takeaways:
- Evidence from randomised trials suggests GLP-1 receptor agonists are unlikely to meaningfully increase or reduce the risk of most obesity-related cancers.
- For several cancer types, including colorectal, liver and endometrial cancer, the certainty of evidence remains low due to limited follow-up.
- Researchers emphasise the need for longer-term studies with cancer-specific outcomes to fully understand potential risks or protective effects.
A comprehensive systematic review published online on 8 December in Annals of Internal Medicine suggests that glucagon-like peptide-1 receptor agonists, commonly known as GLP-1 RAs, have little or no effect on the risk of developing cancers associated with obesity.
The review was led by Albert Ko, MD, of the Harvard T.H. Chan School of Public Health in Boston, and examined data from randomised, placebo-controlled trials involving people treated with GLP-1 RAs for type 2 diabetes or overweight and obesity. While these medications have transformed metabolic care in recent years, concerns have persisted about their long-term safety, including potential cancer risk.
Scope and purpose of the review
GLP-1 receptor agonists are widely prescribed for glycaemic control and weight management, yet their association with cancer has remained uncertain. To address this gap, the researchers conducted a systematic review and meta-analysis to assess whether treatment with GLP-1 RAs is associated with an increased or reduced risk of obesity-related cancers.
The review focused on cancers known to have strong links with excess adiposity, including thyroid, pancreatic, colorectal, gastric, oesophageal, liver, gallbladder, breast, ovarian, endometrial and kidney cancers. It also included multiple myeloma and meningioma.
Data sources and study selection
The authors searched PubMed, Embase, Web of Science, Scopus and the Cochrane Central Register of Controlled Trials from database inception through to August 2025. Only randomised, placebo-controlled trials reporting at least one of the specified cancer outcomes were eligible for inclusion.
In total, 48 trials met the inclusion criteria, encompassing 94,245 participants. None of the trials had been specifically designed to evaluate cancer outcomes, and follow-up durations were generally short.
Methods and quality assessment
Risk of bias across the included trials was assessed using the Cochrane Risk of Bias 2 tool. The certainty of evidence for each outcome was evaluated using the GRADE framework, which considers factors such as study limitations, consistency of results and precision of estimates.
Pooled odds ratios were calculated using random-effects meta-analysis to account for variation between studies.
Main findings by cancer type
The analysis found that GLP-1 receptor agonists probably have little or no effect on the risk of several common obesity-related cancers, based on evidence of moderate certainty.
Specifically:
- Thyroid cancer showed no clear association with GLP-1 RA use, with an odds ratio of 1.37 (95% CI, 0.82 to 2.31), corresponding to between one fewer and nine more cases per 10,000 people treated.
- Pancreatic cancer risk was similarly unaffected, with an odds ratio of 0.84 (95% CI, 0.53 to 1.35), equating to nine fewer to six more cases per 10,000 people.
- Breast cancer showed an odds ratio of 0.95 (95% CI, 0.60 to 1.49), indicating no meaningful difference in risk.
- Kidney cancer also demonstrated no significant association, with an odds ratio of 1.12 (95% CI, 0.78 to 1.60).
For other cancers, including colorectal, oesophageal, liver, gallbladder, ovarian and endometrial cancer, as well as multiple myeloma and meningioma, the evidence suggested little or no effect. However, the certainty of this evidence was rated as low.
For gastric cancer, the findings were described as very uncertain, reflecting sparse data and wide confidence intervals.
Consistency across analyses
The results remained consistent across multiple sensitivity and subgroup analyses. These included analyses restricted to trials with a low risk of bias, studies involving newer agents such as semaglutide or tirzepatide, and comparisons across different follow-up durations, populations, GLP-1 RA classes, doses, weight-loss profiles and durations of action.
This consistency strengthens confidence that the observed lack of association is not driven by a specific drug, dose or patient group.
Limitations of the evidence
The authors highlight important limitations that temper the conclusions. Most notably, the included trials were not designed to detect cancer outcomes and generally had relatively short follow-up periods. As a result, rare cancers or effects that emerge only after prolonged exposure may not have been captured.
Implications and next steps
Summarising the findings, the authors conclude that GLP-1 receptor agonists “may have little or no effect on risk for obesity-related cancers,” while emphasising the need for further research. As they write, “These findings offer important insights into the safety of GLP-1 RAs but highlight the need for longer-term studies with cancer-specific end points to clarify potential risks or protective effects.”
For clinicians and people considering or already using GLP-1 receptor agonists, the review provides a degree of reassurance regarding cancer risk in the short to medium term. However, ongoing surveillance and dedicated long-term studies will be essential as use of these medications continues to expand globally.
Read More
Metabolic Bariatric Surgery Shows Greater Two-Year Weight Loss Than GLP-1 RAs
Key Takeaways:
- Metabolic bariatric surgery was associated with substantially greater and more durable weight loss over two years than treatment with GLP-1 receptor agonists in adults living with class II or III obesity.
- Overall health care costs over two years were lower for people who underwent surgery, largely due to the ongoing pharmacy costs associated with GLP-1 receptor agonist therapy.
- The findings underline the importance of multidisciplinary care, particularly for clinicians managing obesity-related conditions where sustained weight reduction is central to disease control.
Overview
A large retrospective, claims-based cohort study has found that metabolic bariatric surgery delivers greater long-term weight loss benefits and lower overall health care costs over two years compared with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults living with severe obesity. The analysis suggests that, in real-world clinical practice, surgical approaches may offer more durable outcomes than pharmacotherapy alone for this population.
Study design and data sources
This retrospective cohort study compared outcomes following metabolic bariatric surgery with those achieved using GLP-1 receptor agonist therapy for weight management. Surgical procedures included sleeve gastrectomy and gastric bypass. Pharmacological treatments included dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide.
The analysis drew on data from the Highmark Health insurance claims database linked with electronic health records from the Allegheny Health Network. In total, 30,458 adults living with class II or III obesity were included. All individuals in the weight-loss analysis had a body mass index of at least 40 at the time of enrolment.
To minimise baseline differences between groups, the researchers used propensity score weighting to balance key characteristics, including body mass index, age, sex, comorbid conditions, and patterns of health care utilisation. Adjusted analyses then compared weight-loss trajectories, obesity-related comorbidities, and total health care costs over a two-year follow-up period.
Weight loss outcomes and durability
Of the total cohort, 14,101 people underwent metabolic bariatric surgery, with a mean follow-up of 34 months. A further 16,357 people were prescribed GLP-1 receptor agonists, with a mean follow-up of 32 months.
After two years, metabolic bariatric surgery was associated with markedly greater mean total weight loss than GLP-1 receptor agonist therapy, at 28.3 per cent compared with 10.3 per cent. Weight loss following surgery was also more durable. Ninety-six per cent of people in the surgical group achieved sustained weight loss of at least 10 per cent, compared with 46 per cent of those treated with GLP-1 receptor agonists.
In addition to superior weight outcomes, people who underwent metabolic surgery experienced fewer obesity-related comorbidities and lower health care utilisation across inpatient, outpatient, and emergency care settings.
Cost analysis
Over the two-year follow-up period, metabolic bariatric surgery was associated with significantly lower mean total health care costs than GLP-1 receptor agonist therapy. Average costs were reported as $51,794 for the surgical group compared with $63,483 for those receiving GLP-1 receptor agonists.
The higher costs observed in the pharmacotherapy group were largely driven by ongoing pharmacy expenses related to long-term GLP-1 receptor agonist use. While surgery involves a higher upfront cost, the findings suggest this is offset over time by reduced medication use and lower overall health care utilisation.
Study limitations
The authors note several important limitations. Weight data were available for only a small proportion of participants, comprising 9 per cent of the surgery group and 1.6 per cent of the GLP-1 receptor agonist group. This limits the generalisability of the weight-loss findings to the full cohort.
In addition, the indication for GLP-1 receptor agonist prescriptions was not always clear, meaning some individuals may have been treated primarily for diabetes rather than obesity. However, an obesity-only subgroup analysis restricted to people without a diabetes diagnosis produced similar results, supporting the robustness of the main findings.
Follow-up duration differed slightly between groups, and adherence to GLP-1 receptor agonist therapy was likely lower in this real-world setting than would be expected in a controlled clinical trial. Finally, the cost data reflect the United States health care system and may not be directly transferable to other countries or funding models.
Clinical relevance
For clinicians managing obesity-related complications, including ophthalmologists caring for people with obesity-associated eye disease such as idiopathic intracranial hypertension, these findings highlight the broader systemic benefits of durable weight reduction. Although GLP-1 receptor agonists are increasingly recommended in the management of idiopathic intracranial hypertension, the study suggests that metabolic bariatric surgery may offer greater sustained weight loss at a lower long-term cost.
The results emphasise the value of close collaboration between ophthalmology, endocrinology, and bariatric surgery teams when supporting people whose disease burden is driven by obesity. While ongoing government discussions around medication pricing may influence future cost-effectiveness analyses, the substantial differences observed in this study indicate that metabolic surgery is likely to remain a cost-effective intervention even if GLP-1 receptor agonist costs were to decrease.
Disclosures and publication details
Financial disclosures: Dr Chantal Boisvert reports a financial relationship with Viridian Therapeutics, serving as a consultant or advisor and receiving grant support.
Read More
Manchester Launches Landmark Five-Year Mounjaro Trial to Assess Real-World Outcomes
Key Takeaways:
- A five-year real-world trial in Greater Manchester will evaluate the long-term health, employment, and quality-of-life effects of the anti-obesity medication tirzepatide.
- Up to 3,000 people will participate, with recruitment taking place through GP practices to reflect everyday clinical conditions.
- The study is part of a £279 million partnership between Eli Lilly and the UK government aimed at addressing obesity and improving population health.
Introduction: A major real-world test of tirzepatide
A five-year clinical study has begun in Greater Manchester to examine the real-world effectiveness of the anti-obesity medication tirzepatide, marketed in the United Kingdom as Mounjaro. The trial aims to understand how the treatment affects long-term health outcomes when delivered through primary care. The first participants have now been enrolled after visiting their GP, marking the formal start of the project.
Scope and scale of the trial
Up to 3,000 people are expected to take part in what is described as a first-of-its-kind real-world study. The trial forms part of a broader £279 million initiative jointly developed by US pharmaceutical company Eli Lilly and the UK government. The aim is to evaluate new ways of addressing major public health challenges, including obesity and related long-term conditions.
Professor Martin Rutter, professor of cardiometabolic medicine at the University of Manchester, emphasised the focus on early intervention. He explained that the research will assess “how effective early intervention is in tackling obesity”, and will examine a wide range of clinical and social outcomes.
What is tirzepatide?
Tirzepatide is an injectable medication that works by mimicking a hormone that helps people feel fuller for longer, thereby suppressing appetite. While marketed as Mounjaro in the UK, it is sold under the brand name Zepbound in the United States.
Clinical trials have previously shown that people receiving Mounjaro experienced up to 20 percent weight loss after 72 weeks of treatment. The Greater Manchester study will build on this evidence by measuring how the medication performs in routine practice rather than controlled trial conditions.
Real-world outcomes beyond weight
A distinctive feature of the trial is its focus on long-term and practical indicators of wellbeing. Researchers will assess health metrics but will also study broader outcomes such as employment status, sick-day absences, and quality of life. These measures are particularly relevant given the significant economic and social impact of obesity.
According to Health Secretary Wes Streeting, illnesses linked to obesity currently cost the NHS £11 billion annually. In Greater Manchester alone, approximately 600,000 adults live with obesity, said Mark Fisher, chief executive officer of the NHS Greater Manchester Integrated Care Board.
A 2023 report by Health Innovation Manchester also estimated that obesity costs the region more than £3 billion each year when NHS treatment, social care, and the impact on quality of life are taken into account.
Role of primary care in the study
The trial is major in part because it is being delivered through GP practices, providing insights into how tirzepatide performs when prescribed in everyday settings. Dr Imran Ghafoor, GP Partner at Peterloo Medical Centre in Middleton, highlighted the importance of local trust and accessibility. He stated that patients see their GP practice as a “familiar and accessible space”, adding that the research will help “test solutions tailored to real lives”.
As medications like tirzepatide move further into everyday primary care, building healthcare professionals’ understanding of how these drugs work and where they fit in treatment pathways is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course.
A diverse participant group
Professor Rutter, who also serves as the trial’s chief investigator, noted that the study intends to evaluate the medication’s health effects “in a diverse group of individuals”. This emphasis on diversity aims to ensure that the findings reflect the varied experiences of people living with obesity across the region.
CCH insight
Trials like this reflect how central GLP-1 medications have become to obesity care in everyday primary care – and how much rests on the professionals delivering them understanding the science behind them. CCH’s GLP-1RAs in Focus – Why Drugs Like Ozempic Work CPD short course (2 CPD hours, fully online, CPD-accredited) gives healthcare professionals, whether or not they prescribe, a clear grounding in how drugs like tirzepatide work, where they fit in NHS treatment pathways, and how to weigh the evidence with confidence.
Explore GLP-1RAs in Focus →
Study Suggests GLP-1 Medications May Reduce Frailty Progression in Older Adults
Key Takeaways:
- Older adults with type 2 diabetes who begin SGLT-2 inhibitors or GLP-1 receptor agonists show slower frailty progression over one year compared with those starting other diabetes therapies.
- The analysis, based on a large national Medicare dataset, suggests these medications may offer benefits beyond glycaemic and cardiovascular control, potentially supporting strength, mobility, and functional independence.
- The protective effect was not fully explained by fewer cardiovascular or safety events, indicating a possible direct influence of these drug classes on frailty itself.
Emerging evidence that newer diabetes drugs may protect against frailty
A new study has found that older adults living with type 2 diabetes who initiate treatment with sodium–glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists experience significantly slower progression of frailty over a 12-month period compared with those starting alternative diabetes medications. The findings point to a potential added advantage of these therapies in helping older adults maintain physical resilience, strength, and independence, complementing their established effects on blood glucose regulation and cardiovascular risk reduction.
Study overview and methods
The research, published in Diabetes Care and titled “Sodium–Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Frailty Progression in Older Adults With Type 2 Diabetes”, examined a large national cohort of older adults in the United States who had recently begun different classes of diabetes medication.
The investigators analysed a 7 per cent sample of Medicare claims data, enabling real-world tracking of over one year of health outcomes. Frailty progression was assessed using a validated claims-based Frailty Index (CFI), which ranges from 0 to 1 and reflects the cumulative presence of age-related health deficits. Higher CFI scores indicate more severe frailty.
Key findings – slower frailty progression with SGLT-2 and GLP-1 therapies
Older adults newly prescribed a GLP-1 receptor agonist, such as semaglutide (Ozempic) or liraglutide (Victoza), demonstrated a mean CFI change of –0.007 (95 per cent CI: –0.011 to –0.004) compared with matched new users of DPP-4 inhibitors. Those initiating SGLT-2 inhibitors, including empagliflozin (Jardiance) and dapagliflozin (Farxiga), experienced a mean change of –0.005 (95 per cent CI: –0.008 to –0.002).
These figures represent a statistically significant slowing in frailty progression over the study period. In contrast, people beginning sulfonylureas did not show a meaningful difference relative to DPP-4 inhibitor users.
Importantly, the study found that cardiovascular events and other safety-related health issues explained only a small proportion of the protective association. This suggests that these classes of medications may exert a more direct biological effect on mechanisms related to frailty, such as inflammation, physical function, or metabolic stress.
Why frailty matters in older adults with type 2 diabetes
Frailty is common among older adults and especially prevalent in people living with type 2 diabetes. Previous research indicates that 10–15 per cent of adults over the age of 65 meet criteria for frailty, with substantially higher rates among those with diabetes. Multiple factors contribute to this increased vulnerability, including chronic low-grade inflammation, accelerated muscle loss, cardiovascular disease, and the overall physiological strain of managing a long-term condition.
Frailty is linked to an elevated risk of falls, disability, hospital admission, diminished quality of life, and reduced survival. Because frailty is difficult to reverse once it becomes established, clinicians and researchers have prioritised strategies that can delay or slow its progression. The study’s findings therefore hold particular significance for geriatric diabetes care.
Clinical implications – a possible shift in medication decision-making
The results may encourage clinicians to consider the broader health trajectory of older adults when selecting diabetes medications, especially as SGLT-2 inhibitors and GLP-1 receptor agonists are increasingly used for combined glycaemic, cardiovascular, and renal protection.
Chanmi Park, MD, MPH, the study’s lead author and Assistant Scientist I at the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, highlighted this point:
“While SGLT-2 inhibitors and GLP-1 receptor agonists are primarily prescribed for blood sugar control and heart protection, our findings show they may also help older adults with diabetes stay stronger and less vulnerable to health setbacks. Because frailty is common, serious, and hard to reverse, this could meaningfully change how clinicians think about medication choices for ageing patients.”
A promising step towards more holistic diabetes care
The study adds to a growing body of literature suggesting that newer diabetes medications may offer multidimensional benefits. By potentially supporting physical resilience in addition to metabolic and cardiovascular health, SGLT-2 inhibitors and GLP-1 receptor agonists could become central tools in promoting healthier ageing for people living with type 2 diabetes.
Further research will be needed to better understand the biological mechanisms at play and to determine whether similar benefits appear in more diverse patient populations and longer-term studies.
CCH insight:
The results of this study are very encouraging from the perspective of GLP-1 medications and muscle mass/strength. There are currently concerns in some quarters about potential excess loss of muscle mass and sarcopenia accompanying weight loss from these drugs. However, this study points towards a positive impact on physical strength and function from GLP-1 therapy.
Read More
WHO Warns of Severe Global Shortages of GLP-1 Obesity Medicines as Demand Surges
Key Takeaways:
- Fewer than one in ten people worldwide who could benefit from GLP-1 medicines such as Wegovy and Mounjaro are currently able to access them, due to major limitations in production, affordability, and health system readiness.
- The World Health Organization has issued its first formal guidance on the clinical use of GLP-1 therapies, describing them as “a new chapter” in the treatment of obesity, but emphasising the need for equitable access and comprehensive lifestyle support.
- Without urgent action, global obesity prevalence is projected to double to two billion people by 2030, with associated economic costs reaching three trillion US dollars.
WHO Issues first guidance on GLP-1 medicines amid severe supply constraints
The World Health Organization has warned that fewer than one in ten people globally who could benefit from modern GLP-1 obesity medicines are currently able to obtain them, despite the scale of the obesity epidemic and the transformative clinical potential of drugs such as Wegovy and Mounjaro.
With more than one billion people worldwide now living with obesity, the WHO has called for far more widespread, affordable, and equitable access to GLP-1 therapies. Projections indicate that more than two billion people will be living with obesity by 2030 unless governments implement decisive action. The economic burden is expected to rise steeply, with global costs anticipated to reach three trillion US dollars by the same date.
Dr Tedros Adhanom Ghebreyesus, WHO Director-General, stressed that modern pharmacological treatments must be understood as part of a long-term care approach. He stated: “Our new guidance recognises that obesity is a chronic disease that can be treated with comprehensive and lifelong care. While medication alone will not solve this global health crisis, GLP-1 therapies can help millions overcome obesity and reduce its associated harms.”
The WHO has already added GLP-1 medicines to its essential medicines list for people who are overweight and living with diabetes, signalling that countries are advised to provide access to them. The organisation’s new guidance, described as a “special communication” aimed at clinicians, sets out for the first time its formal position on the value, limitations, and safe use of these drugs.
A new chapter in obesity treatment
The WHO notes that GLP-1 therapies represent “more than a scientific breakthrough”. They mark a decisive shift in how obesity is conceptualised, moving away from viewing it solely as a “lifestyle condition” and towards recognising it as a complex, preventable, and treatable chronic disease. The statement published in the Journal of the American Medical Association asserted: “GLP-1 therapies … have emerged as an important innovation in addressing the global obesity challenge. The advent of these medications represents a tipping point in the treatment of obesity, its complications and related co-morbidities.”
The WHO highlighted increasing evidence that GLP-1 therapies may also reduce the risk of several serious conditions, including heart attacks, strokes, type 2 diabetes, high blood pressure, elevated cholesterol, sleep apnoea, and kidney and arterial disease.
However, the organisation emphasised that these medicines must always be paired with holistic support. Individuals prescribed GLP-1s should receive advice on nutrition, physical activity, and behavioural counselling to maintain weight loss and improve long-term health outcomes. The WHO also reiterated that pregnant women should not use GLP-1 therapies.
Global access limited by production, affordability, and system capacity
Despite rising demand, global production capacity remains a major barrier. The WHO estimates that even under the most optimistic forecasts, manufacturers could produce enough GLP-1 medicines for only about 100 million people. This represents less than 10 per cent of the more than one billion who could benefit.
High prices, limited manufacturing capability, and supply chain constraints all significantly restrict access. The WHO has urged pharmaceutical companies to expand production rapidly and to reduce the prices of medications such as Mounjaro and Ozempic to prevent people in low-income countries from being excluded.
The guideline calls for measures such as voluntary licensing, through which patent-holding companies allow other manufacturers to produce low-cost generic versions. This pathway may soon become more viable as key patents expire. The patent on semaglutide, the active ingredient in Novo Nordisk’s Wegovy, is due to expire in several countries in 2026. Once this occurs, manufacturers in India, Canada, China, Brazil, Turkey, and other jurisdictions will be able to develop and sell more affordable versions.
The WHO also underscored three persistent barriers that must be addressed to achieve global access:
- Limited production capacity, availability, and affordability.
- Health system readiness to prescribe and monitor the medicines.
- Universal access to healthcare services.
Dr Tedros stressed the organisation’s “greatest concern is equitable access”.
Calls for national action on prevention and supportive environments
While pharmacotherapy can assist individuals living with obesity, the WHO stated that countries must continue to prioritise prevention and create healthier environments. This includes promoting physical activity, improving food systems, and ensuring that population-level interventions accompany advances in medical treatment.
How GLP-1 obesity medicines work
GLP-1 medicines work by mimicking a natural hormone that slows digestion, suppresses appetite, and increases feelings of fullness. This results in people eating less and typically losing weight within a few weeks of starting treatment.
In the United Kingdom, GLP-1 medicines are prescription-only and can only be supplied following clinical assessment by a healthcare professional. Some formulations are available through the NHS, although many are obtained privately. A black market for these medicines exists, and the WHO and UK regulators warn that people should avoid unregulated sources such as beauty salons or social media sellers.
Research suggests that people often regain much of the weight within a year after stopping GLP-1 therapy, as physiological hunger cues return. This further reinforces the need for comprehensive, long-term behavioural support.
Global obesity burden and associated risks
Obesity affects people in every country and was associated with 3.7 million deaths worldwide in 2024, according to the WHO. Being overweight or living with obesity increases the risk of numerous serious health conditions, including type 2 diabetes, cardiovascular disease, stroke, and several cancers. The WHO’s statement highlights the immense public health implications if access to effective interventions continues to lag far behind global need.
Expert commentary
The WHO statement was authored by senior clinicians Francesca Celletti, Luz De Regil, and Jeremy Farrar, the organisation’s Assistant Director for Health Promotion and Disease Prevention and Control. Dr Farrar formerly served as WHO Chief Scientist and Director of the Wellcome Trust in London.
Katherine Jenner, Executive Director of the United Kingdom’s Obesity Health Alliance, emphasised that medicines are only part of the solution. She stated: “Weight loss drugs have an important role to play, but they are not a silver bullet. In the United Kingdom right now, access is still limited, supply is fragile, and NHS use is tightly targeted. These powerful medicines can help individuals with chronic obesity, but they are not suitable for everyone and must be accompanied by comprehensive support to be used safely and effectively. Evidence shows that most people regain weight once they stop taking these drugs, and we cannot medicate two-thirds of the population indefinitely.”
CCH insight:
The limited supply of GLP-1 medicines globally is of course frustrating, but until new drugs come to market, and just liraglutide, semaglutide and tirzepatide available, this is likely to continue. All three of these drugs are polypeptides, delivered via injection ‘pens’ and must be refrigerated, so they are expensive and complicated to produce. However, new GLP-1 medications are in development which should improve access and reduce costs, such as orforglipron – a small molecule which is easier to produce and can be taken orally in pill form.
Read More